Objectives: Multiple single nucleotide polymorphisms (SNPs) have been identified as risk loci for type 2 diabetes (T2DM). This study was conducted to increase our understanding of the mechanisms through which three novel risk variants affect the risk of T2DM. Methods: 918 Chinese volunteers from Pudong New Area of Shanghai, China, were recruited in Oct-Dec, 2006. Collection of demographic and lifestyle characteristics, body measurements, bio-specimen collection and biochemistry assays were performed during the period. Genotyping of rs290487 at transcription factor 7-like 2 (TCF7L2), rs9465871 at cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1(CDKAL1) and rs1359790 at chromosome 13q31.1 were conducted using Taqman approach. Results: Genotypes of TCF7L2-rs290487, CDKAL1-rs9465871 and rs1359790 at 13q31.1 were not associated with metabolic syndrome or its components. While average levels of glycosylated hemoglobin A1c (HbA1c), fasting glucose, serum lipids and anthropometrics did not differ by genotypes of TCF7L2-rs290487 and rs1359790 at 13q31.1, HbA1c level varied significantly by genotypes of CDKAL1-rs9465871, particularly among women. After adjusting for age, women carrying C allele had a higher level of HbA1c than those bearing T allele, with each C allele linking to appropriate 0.1% increase of HbA1c level (P for trend=0.025). However, the difference was no longer significant after multiple comparison correction. Similar patterns were consistently observed regardless of levels of energy, dietary fat and average glycemic index intake (P for interaction >0.05). Conclusions: CDKAL1-rs9465871 may slightly affect glycemic phenotypes in non-diabetic Chinese women. Our results support the potential role of CDKAL1 gene in the regulation of insulin secretion.